TY - JOUR
T1 - Modeling Hippocampal CA1 Gabaergic Synapses of Audiogenic Rats
AU - Pena, Rodrigo F.O.
AU - Ceballos, Cesar Celis
AU - De Deus, Júnia Lara
AU - Roque, Antonio Carlos
AU - Garcia-Cairasco, Norberto
AU - Leão, Ricardo Maurício
AU - Cunha, Alexandra Olimpio Siqueira
N1 - Publisher Copyright:
© 2020 World Scientific Publishing Company.
PY - 2020/5/1
Y1 - 2020/5/1
N2 - Wistar Audiogenic Rats (WARs) are genetically susceptible to sound-induced seizures that start in the brainstem and, in response to repetitive stimulation, spread to limbic areas, such as hippocampus. Analysis of the distribution of interevent intervals of GABAergic inhibitory postsynaptic currents (IPSCs) in CA1 pyramidal cells showed a monoexponential trend in Wistar rats, suggestive of a homogeneous population of synapses, but a biexponential trend in WARs. Based on this, we hypothesize that there are two populations of GABAergic synaptic release sites in CA1 pyramidal neurons from WARs. To address this hypothesis, we used a well-established neuronal computational model of a CA1 pyramidal neuron previously developed to replicate physiological properties of these cells. Our simulations replicated the biexponential trend only when we decreased the release frequency of synaptic currents by a factor of six in at least 40% of distal synapses. Our results suggest that almost half of the GABAergic synapses of WARs have a drastically reduced spontaneous release frequency. The computational model was able to reproduce the temporal dynamics of GABAergic inhibition that could underlie susceptibility to the spread of seizures.
AB - Wistar Audiogenic Rats (WARs) are genetically susceptible to sound-induced seizures that start in the brainstem and, in response to repetitive stimulation, spread to limbic areas, such as hippocampus. Analysis of the distribution of interevent intervals of GABAergic inhibitory postsynaptic currents (IPSCs) in CA1 pyramidal cells showed a monoexponential trend in Wistar rats, suggestive of a homogeneous population of synapses, but a biexponential trend in WARs. Based on this, we hypothesize that there are two populations of GABAergic synaptic release sites in CA1 pyramidal neurons from WARs. To address this hypothesis, we used a well-established neuronal computational model of a CA1 pyramidal neuron previously developed to replicate physiological properties of these cells. Our simulations replicated the biexponential trend only when we decreased the release frequency of synaptic currents by a factor of six in at least 40% of distal synapses. Our results suggest that almost half of the GABAergic synapses of WARs have a drastically reduced spontaneous release frequency. The computational model was able to reproduce the temporal dynamics of GABAergic inhibition that could underlie susceptibility to the spread of seizures.
KW - CA1 pyramidal cells
KW - Wistar audiogenic rats
KW - inhibitory postsynaptic currents
KW - interevent interval
KW - release frequency
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UR - http://www.scopus.com/inward/citedby.url?scp=85084380099&partnerID=8YFLogxK
U2 - 10.1142/S0129065720500227
DO - 10.1142/S0129065720500227
M3 - Article
C2 - 32285725
AN - SCOPUS:85084380099
SN - 0129-0657
VL - 30
JO - International journal of neural systems
JF - International journal of neural systems
IS - 5
M1 - 2050022
ER -